Compositions and methods for treating hoof diseases

ABSTRACT

The present invention is generally directed to compositions and methods for the treatment of an infectious disease of the foot of an animal. One aspect of the invention is directed to a method for preventing and/or treating one or more infectious diseases of the hoof in animals, comprising: preparing a copper-free and zinc-free composition comprising at least one cross-linking agent, wherein the cross-linking agent is not formaldehyde; and administering the composition to a lower leg and hoof area of said animal to prevent and/or treat said one or more infectious diseases. Another aspect of the invention is directed to a copper-free and zinc-free composition for the treatment and/or prevention of one or more infectious diseases of the hoof in animals, comprising at least one cross-linking agent, wherein said cross-linking agent is not formaldehyde. The present invention is also directed to a method for treating and/or preventing papillomatous digital dermatitis in an ungulate, comprising: preparing a copper-free and zinc-free composition comprising at least one cross-linking agent and at least one quaternary ammonium compound; and spraying or applying in a foam a therapeutically effective amount of said composition to a lower leg and hoof area of said ungulate in order to treat and/or prevent said papillomatous digitial dermatitis.

1. CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 12/626,302, filed Nov. 25, 2009, which claims priority to U.S.Provisional Application No. 61/200,367, filed Nov. 28, 2008. All priorapplications listed are hereby incorporated by reference in theirentirety.

2. TECHNICAL FIELD

The present invention relates to the treatment of a diseased animal. Inparticular, the present invention relates to compositions and methodsuseful for the treatment of one or more infectious diseases of a foot ofan animal.

3. BACKGROUND OF THE INVENTION

Diseases among dairy herds dramatically impact the economics of animalproduction and milk production in the United States. It is estimatedthat the dairy cattle industry constitutes a significant contribution tothe gross national product of the United States, accounting for anestimated $38 billion annually. A wide range of diseases, infections andinjuries to the feet of animals, including cattle that are part of dairyherds, exist. Livestock in a dairy herd, for example, are susceptible toforming a variety of warts, abscesses, sole ulcers, foot rot, heelcracks and variations of lesions and infections on their feet and/orhooves, which may individually or collectively cause livestock to sufferlameness, clubbed hooves, loss of body weight, decreased milkproduction, and decreased rates of conception.

Infectious hoof diseases are common in farm animals such as sheep,goats, horses, dairy cows, and beef cattle. For example, hairy hoofwarts, also referred to as digital dermatitis, hairy footwarts,strawberry or raspberry heelwarts or hairy heel warts, is a commondisease condition in dairy cows and can cause lameness which leads to adecline in animal health and performance as measured by a decrease inbody weight, fertility, and milk production. Since the late 1980's,bacterial diseases such as hairy heel warts have been a significantsource of bovine lameness, and have had a significant economic impact onfarmers.

Farmers have addressed this problem using a livestock footbath. Thefootbath holds a solution containing a substance to prevent and/or treatthe disease, such as copper sulfate and/or zinc sulfate, or anantibiotic. Animals are forced to walk through the footbath to immersethe hooves in the treatment solution. For example, dairy cattle areusually led through a footbath on their way to or from the milkingparlor. However, there are problems associated with the use of livestockfootbaths, and they are not the most effective method of treatment andprevention of foot diseases. In particular, foot baths are inefficientand costly for at least one of the following reasons.

First, the length of the foot bath is directly correlated to theeffectiveness of the treatment solution, with the longer the bath, thegreater the duration of exposure to the treatment and preventionsolution. The commonly used four foot long baths are not long enough forproper cleaning of the feet and subsequent exposure of the lesions tothe treatment solution, especially since on average, animals walkthrough a traditional foot bath for five seconds or less. Moreover,manure attached to the animals hooves will commonly be carried into thefoot bath or the animal may defecate into the foot bath, and since footbaths are liquid filled reservoirs that hold all environmentalcontaminants, the manure, mud and dirt rapidly degrade the treatmentsolution and render it ineffective. Also, most foot baths arepermanently fixed and this prevents a farmer from locating the bath andtreating the animals at different locations on the facility.

A further limitation to use of foot baths on farms is that they requirea high level of management. The treatment solution requires changing atspecified intervals after several animals pass through the bath in orderto maintain efficacy of the treatment solution. If the foot bath is notchanged and re-charged accordingly, the efficacy of the treatmentsolution is greatly reduced. On a practical level, animals experiencingfoot problems generally walk slower and are the last animals through thefoot bath, when the bath is at its most inefficient, thereby decreasingthe effectiveness of the treatment. Yet another limitation associatedwith the use of foot baths is that many of the products available forthe treatment and prevention of foot diseases are not labeled for use infoot bath applications and are difficult to get into solution, forexample, copper sulfate and zinc sulfate. Other products, includingantibiotics, are not easy to use in the context of a foot bath,especially due to their cost and the fact that antibiotics degradequickly when exposed to organic material.

Moreover, such footbaths as described supra may also cause pollution andinjury to animals and humans. For example, discharge of copper sulfate,a compound commonly used in treating cows, from bath treatment systemsinto adjacent lands may cause significant damage. This is because mostdairies dump the spent foot baths into a manure pit or a lagoon and thecopper ultimately gets spread on production ground with the manure. Thepractice can lead to copper accumulation in the soil and after severalyears can accumulate in soil to levels that become toxic to soilmicrobes and crops. This can slow organic matter decomposition andnutrient cycling in soil and crop production could be reduced because ofdirect toxic effects of copper on the plants as well as reduced soilfertility. Importantly, copper accumulation in soil and forage canbecome toxic to sheep, whose tolerance for copper is much lower thanthat of dairy cattle. Toxic levels of copper in soil is a critical issuebecause there is no practical way to reverse the problem. Moreover, manylarge dairy farms use anaerobic digesters to produce methane gas frommanure, and when copper sulfate can inhibit the bacteria's ability toproduce methane gas in a digester lagoon.

Another chemical used in foot baths by the dairy industry isformaldehyde. Numerous burns to humans and animals result annually fromuse of formaldehyde; loss of eyesight and even death among workers haveoccurred. For these reasons the European Union has called for a ban ofits use, and in the United States it has been listed as a knowncarcinogen.

In view of the problems outlined supra, there is a need for improvedcompositions and methods for treating one or more infectious diseases ofa foot of an animal, including hairy heel warts.

4. SUMMARY OF THE INVENTION

The present invention is generally directed to compositions and methodsfor the treatment of an infectious disease of the foot of an animal. Ithas been surprisingly discovered that a spray or foam application of thepresently taught novel and useful compositions offer more efficient anda better approach to treating one or more infectious diseases of a footof an animal, including hairy heel warts.

One aspect of the invention is directed to a method for preventingand/or treating one or more infectious diseases of the hoof in animals,comprising: preparing a copper-free and zinc-free composition comprisingat least one cross-linking agent, wherein the cross-linking agent is notformaldehyde; and administering the composition to a lower leg and hoofarea of said animal to prevent and/or treat said one or more infectiousdiseases. In one embodiment, the animal has, or is at risk for, aninfectious disease of the foot. In another embodiment, the infectiousdisease of the foot is hairy heel warts, foot rot, stable foot rot, orfoot scald. In a related embodiment, the infection disease ispapillomatous digital dermatitis. In one embodiment, the animal is anungulate. In a related embodiment, the animal is a cow, sheep, horse, orgoat.

In one embodiment, the administering step comprises spraying, splashing,or applying. In another embodiment, the administering step is in theform of a spray or foam, or a mixture thereof. In another embodiment,about three to about ten milliliters of the composition is sprayed on tothe lower leg and hoof area of the animal. In another embodiment, theadministering step is in the form of a gel.

In one embodiment, the infectious disease comprises an open lesion andafter the administering step, said composition facilitates the rapidformation of a scab over said lesion. In another embodiment, theinfectious disease comprises an open lesion on the lower leg and/or hoofarea of said animal, and wherein after the administering step, saidcomposition facilitates the rapid formation of a scab over said lesionwithin about twenty minutes. In one embodiment, the infectious diseasecomprises an open lesion on the lower leg and/or hoof area of saidanimal, and wherein about five to about fifteen minutes after theadministering step, said composition causes the formation of a scab oversaid lesion. In another embodiment, after the administering step, theexposure time of said composition to a lower leg and hoof area of saidanimal is between about 5 to about 30 minutes. In another embodiment,the administering step includes periodic administrations. In oneembodiment, the composition comprises at least one of colorants, skinconditioners, and buffers.

In one embodiment, the cross-linking agent is selected from the groupconsisting of glutaraldehyde, glyoxal, ortho-phthaldehyde,carbodiimides, diisocyanates, a formaldehyde donor, sodium hydroxymethylglycinate, diazolidinyl urea, imidazolidinyl urea,dimethylol-5,5-dimethylhydantoin, dimethylol urea,2-bromo-2-nitropropane 1,3-diol, quaternium-15, parabens,5-chloro-2-methylisothiazolin-3-one, 1,2-dibromo-2,4-dicyanobutane,ethanol and other alcohols, and polyol.

In another embodiment, the cross-linking agent is selected from thegroup consisting of aldehydes, such as glyceraldehyde, glutaraldehyde,dextran dialdehyde, and carbohydrates; diols, such as ethylene glycol,di(ethylene glycol), polyethylene glycol, propylene glycol,di(propylene) glycol, polypropylene glycol; unsaturated diesters such asethylene glycol dimethacrylate, di(ethylene glycol) dimethacrylate,poly(ethylene glycol) dimethacrylate, poly(laurylmethacrylate-co-ethylene glycol dimethacrylate), propylene glycoldimethacrylate, di(propylene glycol) dimethacrylate, polypropyleneglycol) dimethacrylate; dihydrazides such as malonic dihydrazide,ethylmalonic dihydrazide, succinic dihydrazide, glutaric dihydrazide,adipic dihydrazide, isophthalic dihydrazide, oxalyl dihydrazide, pimelicdihydrazide, 3,3′-sulfonyldibenzenesulfonic dihydrazide; diisocyanatessuch as m-xylylene isocyanate, 4-methyl-m-phenylene diisocyanate,2-methyl-m-phenylene diisocyanate, 3,3′-dimethoxy-4,4′-biphenylenediisocyanate, 4-Br-6-methyl-1,3-phenylene diisocyanate,4-Cl-6-methyl-1,3-phenylene diisocyanate, toluene 2,4-diisocyanate,1,3-phenylene diisocyanate, 1,4-phenylene diisocyanate,2,4,6-trimethyl-1,3-phenylene diisocyanate, 1,4-diisocyanatebutane,1,6-diisocyanatehexane, 1,8-diisocyanateoctane, isophorone diisocyanate;carbodiimides such as N,N-(3-dimethylaminopropyl)-N-ethyl carbodiimide(EDC); salts, such as CaCl.sub.2; divinylsulfone, sulfonylurea,hydrolysable polyrotaxane, L-lysine methyl ester, and genipin. In oneembodiment, the one or more cross-linking agents of the presentinvention are present in the composition at a level from 5% to 30%.

In one embodiment, the composition further comprises at least oneantimicrobial essential oil or at least one active thereof or a mixturethereof. In a related embodiment, the antimicrobial essential oil isselected from the group consisting of those obtained from thyme,lemongrass, citrus, lemons, orange, anise, clove, aniseed, pine,cinnamon, geranium, roses, mint, lavender, citronella, eucalyptus,peppermint, camphor, ajowan, sandalwood, rosmarin, vervain, fleagrass,lemongrass, ratanhiae, cedar and mixtures thereof. In another relatedembodiment, the actives of essential oil is selected from the groupconsisting of thymol, eugenol, menthol, geraniol, verbenone, eucalyptol,pinocarvone, cedrol, anethol, carvacrol, hinokitiol, berberine, ferulicacid, cinnamic acid, methyl salicylic acid, methyl salycilate,terpineol, limonene and mixtures thereof. In another embodiment, theantimicrobial essential oil or active thereof or mixture thereof ispresent in the composition at a level from 0.03% to 3%.

In one embodiment, the composition further comprises at least onepoly(alkylene glycol) alkyl ether. In a related embodiment, thepoly(alkylene glycol) alkyl ether is selected from the group consistingof polypropylene glycol) mono butyl ether, poly(ethyleneglycol-co-propylene glycol) mono butyl ether, poly(ethylene glycol)dimethyl ether, poly(ethylene glycol-co-propylene glycol) dimethylether, poly(ethylene glycol) stearate or mixtures thereof. In anotherembodiment, the apoly(alkylene glycol) alkyl ether is present in thecomposition at a level from 0.03% to 3%.

In one embodiment, the composition further comprises at least onegelling agent. In one embodiment, the gelling agent is selected from thegroup consisting of naturally-occurring polymeric materials such aslocust bean gum, guar gum, sodium alginate, sodium caseinate, eggalbumin, gelatin agar, carrageenin gum, sodium alginate, xanthan gum,quince seed extract, tragacanth gum, starch, chemically modifiedstarches, semi-synthetic polymeric materials such as cellulose ethers(e.g. hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose,hydroxy propylmethyl cellulose), hydroxypropyl guar gum, soluble starch,cationic celluloses, cationic guars, carboxyvinyl polymers,polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid polymers,polymethacrylic acid polymers, polyvinyl acetate polymers, polyvinylchloride polymers, acrylic acid/ethyl acrylate copolymers, carboxyvinylpolymers, and polyvinylidene chloride polymers. In another embodiment,the at least one gelling agent comprises naturally-occurring polymericmaterials, chemically modified starches, semi-synthetic polymericmaterials, synthetic polymeric materials, acrylic acid/ethyl acrylatecopolymers and carboxyvinyl polymers.

In one embodiment, the at least one gelling agent is locust bean gum,guar gum, sodium alginate, sodium caseinate, egg albumin, gelatin agar,carrageenin gum, sodium alginate, xanthan gum, quince seed extract,tragacanth gum, starch, a cellulose ether, hydroxypropyl guar gum,soluble starch, cationic cellulose, cationic guar, a carboxyvinylpolymer, polyvinylpyrrolidone, polyvinyl alcohol, a polyacrylic acidpolymer, a polymethacrylic acid polymer, a polyvinyl acetate polymer a,a polyvinyl chloride polymer, a polyvinylidene chloride polymer, apolyalkenyl polyether cross-linked polymer of acrylic acid, or a mixturethereof. In another embodiment, the at least one gelling agent ishydroxypropylmethyl cellulose, hydroxyethyl cellulose, methyl cellulose,carboxymethyl cellulose, or a mixture thereof. In a related embodiment,the gelling agent is xanthan gum. In another embodiment, the gellingagent is present in the composition at a level from 0.03% to 3%.

In one embodiment, the composition further comprises at least onequaternary ammonium compound. In one embodiment, the quaternary ammoniumcompound is selected from the group consisting of quaternary ammoniumcompounds containing alkyl or substituted alkyl groups, alkyl amide andcarboxylic acid groups, ether groups, unsaturated alkyl groups, andcyclic quaternary ammonium compounds. These compounds can be chlorides,dichlorides, bromides, methylsulphates, chlorophenates,cylcohexylsulphamates or salts of the other acids. In anotherembodiment, the quaternary ammonium compound is selected from the groupconsisting of alkylpyridinium chlorides and/or sulphates, the alkylgroup being preferably cetyl, dodecyl or hexadecyl group,alkylisoquinolyl chlorides and/or bromides, the alkyl group beingpreferably dodecyl group, octyl decyl dimethyl ammonium chloride,dioctyl dimethyl ammonium chloride, didecyl dimethyl ammonium chloride,alkyl dimethyl benzyl ammonium chloride, alkyl dimethyl benzyl ammoniumchloride wherein the alkyl is one or more of C₁₂ C₁₄ and C₁₆ alkyl,alkyl dimethyl ammonium saccharinate, cetylpyridinium and mixturesthereof. In one embodiment, the quaternary ammonium compound is selectedfrom the group consisting of n-alkyl dimethly benzyl ammonium chloride,dialkyl dimethly ammonium chloride, or a mixture thereof. In anotherembodiment, the at least one quaternary ammonium compound is present inthe composition at a level from 5% to 20%.

In one embodiment, the composition further comprises at least onesurfactant. In another embodiment, the composition further comprises atleast one surfactant selected from the group consisting of nonionic,semi-polar, anionic, cationic, zwitterionic, and amphoteric surfactants.In another embodiment, the composition further comprises a surfactantselected from the group consisting of polyoxyethylene alcohols, alkylether sulfates, and alkyl sulfates. In another embodiment, thecomposition further comprises about 0.03% to 5% by weight of asurfactant.

In another embodiment, the composition further comprises at least onesurfactant selected from the group consisting of glycoside, glycols,ethylene oxide and mixed ethylene oxide/propylene oxide adducts ofalkylphenols, the ethylene oxide and mixed ethylene oxide/propyleneoxide adducts of long chain alcohols or of fatty acids, mixed ethyleneoxide/propylene oxide block copolymers, esters of fatty acids andhydrophilic alcohols, sorbitan monooleates, alkanolamides, soaps,alkylbenzene sulfonates, olefin sulfonates, paraffin sulfonates,propionic acid derivatives, alcohol and alcohol ether sulfates,phosphate esters, amines, amine oxides, alkyl sulfates, alkyl ethersulfates, sarcosinates, sulfoacetates, sulfosuccinates, cocoamphocarboxyglycinate, salts of higher acyl esters of isethionic acid, salts ofhigher acyl derivatives of taurine or methyltaurine, phenol poly ethersulfates, higher acyl derivatives of glycine and methylglycine, alkylaryl polyether alcohols, salts of higher alkyl substituted imadazoliniumdicarboxylic acids, ferchorics, tannics, naphthosulfonates, laurylsulfate, laurylether sulfate, cocamidopropylbetaine, alkylpolyglycosides, amine oxides, monochloracetics anthraflavinics,hippurics, anthranilics, naphthoics, phthalics, carboxylic acid salts,acrylic acids, phosphates, alkylamine ethoxylates, ethylenediaminealkoxylates, betaines, sulfobetaines, imidazolines, polyoxyethylenealcohols, alkyl ether sulfates, and alkyl sulfates. In one embodiment,the composition further comprises one or more ethoxylated nonlyphenols.

One aspect of the present invention is directed to a copper-free andzinc-free composition for the treatment and/or prevention of one or moreinfectious diseases of the hoof in animals, comprising at least onecross-linking agent, wherein said cross-linking agent is notformaldehyde. In one embodiment, the composition comprises about 5% toabout 30% by weight of at least one cross-linking agent; about 5% to 20%by weight of at least one quaternary ammonium compound; about 0.03% to3% by weight of at least one apoly(alkylene glycol) alkyl ether; about0.03% to 3% by weight of at least one gelling agent; about 0.03% to 3%by weight of at least one antimicrobial essential oil or active thereof;and about 0.03% to 5% by weight of at least one surfactant.

One aspect of the present invention is directed to a composition for thetreatment and/or prevention of one or more infectious diseases of thehoof in animals, comprising one or more cross-linking agents, excludingformaldehyde; one or more quaternary ammonium compounds; one or moregelling agents; one or more surfactants; one or more antimicrobialessential oils or actives thereof; and one or more poly(alkylene glycol)alkyl ethers.

One aspect of the present invention is directed to a method for treatingand/or preventing papilomatous digital dermatitis in an ungulate,comprising: preparing a copper-free and zinc-free composition comprisingat least one cross-linking agent and at least one quaternary ammoniumcompound; and spraying or applying in a foam a therapeutically effectiveamount of said composition to a lower leg and hoof area of said ungulatein order to treat and/or prevent said papillomatous digitial dermatitis.

5. BRIEF DESCRIPTION OF THE FIGURES

The patent or application file contains at least one drawing executed incolor. Copies of this patent or patent application publication withcolor drawing(s) will be provided by the Office upon request and paymentof the necessary fee.

Those of skill in the art will understand that the drawings, describedbelow, are for illustrative purposes only. The drawings are not intendedto limit the scope of the present teachings in any way.

FIG. 1 is a line graph showing the extent of cross-linking of theprotein medium over time where three dilutions of formaldehyde 37% wasused.

FIG. 2 is a line graph showing the extent of cross-linking of theprotein medium over time where three dilutions of glutaraldehyde 50% wasused.

FIG. 3 is a line graph showing the extent of cross-linking of theprotein medium over time where three dilutions of glyoxal 40% was used.

FIG. 4 is a line graph showing the extent of cross-linking of theprotein medium over time where two dilutions of a mixture ofglutaraldehyde 50% and glyoxal 40% at a 1:2 ratio was used, with orwithout a quaternary ammonium compound, QUAT at 10%.

FIG. 5 depicts results from the field testing studies of cows affectedby hairy heel warts, showing the lesion sites before and after treatmentvia spray of the presently taught composition. FIG. 5A to 5C show imagesfrom one cow before (FIG. 5B) and after (FIG. 5C) treatment of thelesion. FIG. 5D to 5F show images from another cow before (FIG. 5E) andafter (FIG. 5F) treatment of the lesion. FIG. 5G to 5I show images fromone cow before (FIG. 5H) and after (FIG. 5I) treatment of the lesion.

6. DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, it has been discovered thatcompositions of the present invention can be used to control diseases ofthe hoof, such as foot warts, hoof rot, and other bacterial hoofconditions more effectively than other products.

It has been discovered that a novel composition and a method ofadministering it is highly effective at treating and/or preventinginfectious diseases of the foot of an animal, including hairy heelwarts. Unlike compositions comprising formaldehyde, the presently taughtcomposition has no obnoxious odors and unlike solutions containingcopper, the present composition is biodegradable. Some of the treatmentsavailable use antimicrobials in footbaths in order to kill the bacteriaassociated with the disease condition, however, once the animal leavesthe footbath, the open wart is prone to being re-infected as the cowwalks into bacteria infested mud and manure.

The presently taught composition possesses germicidal components and areformulated so that after their administration, the compositionfacilitates creation of a natural scab where the infectious disease mayhave caused ulcers. Formation of a scab is important because it stopsthe outward progression of the destructive bacteria, providing a toughwaterproof barrier which prevents contamination and re-infection, andallows the animals' immune system to begin the healing process.Formation of the scab occurs rapidly through a process known ascross-linking which occurs to the protein fibers in the open wound. Oneof the advantageous properties of the presently taught composition overexisting treatments, is the rapid nature in which the compositionpromotes formation of a scab. In addition, unlike other treatments, thepresently taught composition does not affect normal skin.

Infectious diseases of the hoof, such as hairy heel warts (papillomatousdigital dermatitis, or “PDD”) hoof rot (interdigital phlegmon), andstable hoof rot (interdigital dermatitis) are common in farm animalssuch as sheep, goats, horses, dairy cows, and beef cattle. The benefitsof the compositions and methods of the present invention for treatingand/or preventing diseases of the foot of an animal over othercompositions and methods include efficacious non-toxic compositions,maintenance of low levels of infectious diseases, and/or reduced amountsof copper being transferred to the soil and water. In particular, thepresent invention teaches formulating the unique composition in a uniqueway as a spray or foam, and such means of administering the compositionof the present invention has superior benefits to existing methods fortreating and/or preventing diseases of the foot of an animal, includinghairy heel warts.

Hairy heel warts, also referred to as digital dermatitis, hairyfootwarts, strawberry or raspberry heelwarts or hairy hoof warts, is acommon disease condition in dairy cows. These diseases can causelameness, leading to animals walking on toes and decreased body weight,fertility and milk production, with the seriously afflicted animalsbeing culled. Clinically, hairy heel warts typically appear as alameness outbreak of variable severity within dairy herds. It is asuperficial skin disease of the bovine digit with variable presentation,depending on the stage of the lesion, from painful, moist,strawberry-like lesions to raised, hairy, wart-like lesions. Theselesions are generally located on the rear of the foot between the bulbsof the heel. Since the late 1980's, such bacterial diseases have harmedlivestock and have caused significant economic losses for affected dairyproducers.

Hairy heel warts is a contagious disease, based on the spread of diseaseregionally, high levels of disease within affected herds, within-herdspread after introduction of affected cattle, and higher prevalence inyounger cows and that large herd size, the amount of moisture in corralswhere cows walk, and the introduction of dairy replacement heifers arecontributing factors to disease occurrence. The exact causative agentfor hairy heel warts is not known, however evidence suggests that one ormore species of spirochete of the genus Treponema is responsible.Treponema bacteria can be anaerobic or microaerophilic (require oxygenat less than atmospheric levels) and can be parasitic to humans and toanimals causing a range of diseases. Mud and manure slurry found indairy free stall environments are an ideal environment for Treponemabacterial to thrive.

The lesions characteristic of hairy heel warts are generally, but notalways, at the back of the foot near interdigital cleft and heel.Sometimes the lesions are at the front of the foot, in the interdigitalcleft or near dewclaws. An early lesion is sharply demarcated, flat,dime-sized, round to oval, moist, tufted, strawberry-like surface. Amature lesion, however, is larger (up to two inches across), usually israised, and sometimes with long brown/black tufts or hair-like, tissueprojections on the surface. Long hairs can be present on edge of thelesion. The lesions can be very painful to the animal and persist formany months, having direct and indirect physiological effect on theanimal.

Hoof rot, or interdigital phlegmon, is an infection of the soft tissuebetween the claws of the feet. In equine animals, it is also known ashoof thrush. Here, the term “hoof rot” will be used to indicate bothhoof rot and hoof thrush. Hoof rot is caused by the anaerobic bacterium,Fusobacterium necrophorum. The anaerobes Dichelobacter (Bacteriodes)nodosus and Prevotella melaminogenicus have also been implicated. Thebacteria invade the skin of the foot at injured or damaged skin areas,and initially cause a painful swelling of the skin between the claws. Afissure or crack then develops along the swollen area for part or all ofthe length of the interdigital space. If left untreated, hoof rot canenter the joints, bones, and/or tendons of the foot, making recoveryfrom the infection unlikely. Animals with hoof rot can have a mildfever, loss of appetite and accompanying weight loss, and develop mildto severe lameness.

Interdigital dermatitis, or stable hoof rot, is generally a chronicinflammation of the skin in the area between the toes of the feet(interdigital cleft). This infection is caused by the bacteriumDichelobacter nodosus. The skin in the area of the interdigital cleftwill appear puffy with a dry exudation which will cause a crust to form.The condition may occasionally cause lameness or heel crack/heel erosionbut generally results in an alteration in the animal's gait.

Control of hairy warts and associated foot diseases has provendifficult. At present, one effective treatment of hoof warts, hoof rotand stable hoof rot is the use of antibiotics, such as tetracycline,lincomycin, spectinomycin, penicillin, oxytetracycline, and ampicillin,which are topically applied to the affected area via use of footbaths.Most commercial foot baths are thirty inches wide, four feet long andsix inches deep, and require about thirty five gallons of treatmentsolution. Where footbaths are used, the animal is led to walk throughwhile either entering or exiting particular areas, such as for examplemilking parlors, shearing stalls, or feeding stalls, the footbath toimmerse the hooves in a treatment solution, containing an antibiotic orother material such as copper sulfate and/or zinc sulfate.

However, there are problems associated with the use of livestockfootbaths as detailed supra. For example, bacteria-containing organicmaterials on the hooves of the animals are washed off in the footbathsolution. The organic materials build up over time and overcome theability of the material in the solution to prevent and/or treat thedisease. In some cases, the footbath can even become a breeding groundfor bacteria, and can thus actually accelerate the spread of aninfectious hoof disease, rather than treat and/or prevent it.Additionally, disposal of the footbath water may raise environmentalconcerns, as several states are mandating the discontinued use ofproducts containing heavy metals such as copper.

Application of oxytetracycline under a bandage can be effective, butbandaging affected hooves may be labor-intensive in large or heavilyafflicted herds. Even though antibiotics can be effective in treatingthese infectious diseases, there are also several drawbacks to theiruse, including their expense and the concern, especially with dairycows, that the use of antibiotics may result in the presence ofantibiotic residues in the animal or its milk. Further, extended use ofantibiotics may result in the development of an antibiotic-resistantbacteria strain. Finally, the use of antibiotics for the treatment ofhoof rot, stable hoof rot or hairy heel warts is “off-label,” that is,the antibiotics are not specifically approved for these uses.

In order to treat and prevent hoof rot, hairy heel warts, and stablehoof, chemical-based germicides have also been tried as a treatment.Although some germicides, such as those containing copper sulfate andzinc sulfate, have some efficacy against hoof rot and stable hoof rot,they are ineffective against hairy heel warts. Many of the availablecompounds are expensive and/or ineffective at high dilutions, such asthose used in foot baths. Likewise, combinations of hydrogen peroxideand peracetic acid have been used, but also are not effective againsthairy heel warts, and suffer from stability and storage problems, aswell as the problem that the chemical combination irritates the hoof atthe recommended treatment concentrations.

Hairy heel warts have been treated in a number of ways. One form ofcontrol is to treat the larger clinically active lesions, which are asource of infection, by surgical removal, although additional treatmentsfor complete healing may be necessary. This process is laborious, timeconsuming and expensive, particularly when dealing with large herds.There have been anecdotal reports of success with formaldehyde againsthairy heel warts, however, this agent is classified as a carcinogen andtoxin, and is illegal in some parts of the United States. Further, useof too high a concentration of formaldehyde can result in destruction ofhealthy hoof tissue, or can even lead to sloughing of the hoof. Thus,the use of formaldehyde is not desired in treating hairy heel warts andother diseases of the hoof.

The present invention addresses the need for a composition that iseffective against foot rot, stable foot rot, and hairy heel warts, thatis affordable, copper-free and zinc-free, and that avoids the use ofantibiotics. The present invention also addresses the need for aneffective method of both treating and/or preventing foot rot, stablefoot rot, and hairy heel warts. A novel composition has been discoveredwhich is highly effective at treating infectious diseases of the foot ofan animal, including hairy heel warts when applied to the lower leg andhoof area of the animal as a spray or foam. This approach provides amore efficient and selective means by which infectious diseases of thefoot of an animal, including hairy heel warts can be treated and/orprevented in animals, including cows. One of the advantageous propertiesof the presently taught composition is the rapid nature in which thecomposition promotes formation of a scab over a lesion that may haveformed.

One aspect of the present invention is directed to a method forpreventing and/or treating one or more infectious diseases of the hoofin animals, comprising: preparing a copper-free and zinc-freecomposition comprising at least one cross-linking agent, wherein thecross-linking agent is not formaldehyde; and administering thecomposition to a lower leg and hoof area of said animal to preventand/or treat said one or more infectious diseases. The animal has, or isat risk for, an infectious disease of the foot, and the infectiousdisease of the foot is hairy heel warts, foot rot, stable foot rot, orfoot scald. The animal to be treated is commonly a cow, sheep, horse, orgoat.

The method of the present invention includes administering the novelcomposition in the form of a spray or foam, or a mixture thereof.Generally, about three to about ten milliliters of the composition issprayed on to the lower leg and hoof area of the animal, and inparticular to the site of any lesion. The composition may also beadministered in the form of a gel to the lower leg and hoof area of theanimal. Where the infectious disease comprises an open lesion,administration of the composition facilitates the rapid formation of ascab over said lesion, which can occur within about five to aboutfifteen minutes. This rapid formation of a scab is a desirable qualityof the present composition and is achieved in part by the novel means ofadministering the novel composition. The administering step may includeperiodic administrations of the composition, and the composition maycomprise at least one of colorants, skin conditioners, and buffers.

In some embodiments, the animal has, or is at risk for, an infectiousdisease of the foot. As an example, an animal can be in need oftreatment with the compositions described herein when the animal isdiagnosed with hairy heel warts, foot rot, and/or scald. As anotherexample, an animal can be in need of treatment with the compositionsdescribed herein when the animal is determined at risk for hairy heelwarts, foot rot, and/or scald. Diagnosis of infectious diseases of thefoot in animals is within the skill of the art. The determination ofrisk for an infectious disease of the foot can be according toenvironmental conditions, susceptibility of certain types of animals, orother factors known to one of skill in the art.

6.1 DEFINITIONS

As used in this document, the term foot as used in this document meansnot only the terminal part of a vertebrate animal's leg, but also thehoof (the curved covering of horn that protects the front of theterminal part), the pad, the pastern, the dewclaw, the hock, and theportion of the leg below the knee or hock on an animal such as adomestic bovine.

As used herein, treatment is generally understood to encompass bothprophylactic treatment as well as treatment of an existing or diagnosedcondition. For example, an animal in need of treatment can be at risk,or determined to be at risk, for an infection of the foot. As anotherexample, an animal in need of treatment can have, or be diagnosed ashaving, an infection of the foot. Diagnosis and risk assessment foranimal foot diseases discussed herein is within the skill of the art. Insome cases (e.g., with hoof rot), the treatment is preferably toincrease hoof hardness, thus helping to prevent the infection.

The term ungulate is understood to include an animal having hooves, orfeet resembling hooves, or feet that are hoof-like. An ungulate is alsounderstood to include an animal of, or belonging to, the former orderUngulata, now divided into the orders Perissodactyla and Artiodactylaand composed of hoofed mammals such as, but not limited to, a horse, acow, a goat, a sheep, a pig, deer, an elephant, an elk, a bison, amoose, a gazelle, and an antelope. The term debris means at least animalwaste.

The term ingredients means any combination of active and inert chemicalsand fluids, including water, that may be discharged from dispensers fortreating animal foot problems including, without limitations, diseases,infections, abrasions, and injuries to a foot of an animal, as well aspreventative ingredients including, for example, those useful forcreating resistance to diseases and lacerations, for hardening hooves,and similar desirable treatments.

6.2 COMPOSITIONS AND METHODS

The subject invention provides an inexpensive, easy to use, highlyeffective, composition and method of treating and/or preventinginfectious diseases of hoofed animals, including hairy hoof warts. Oneaspect of the present invention is directed to a method for preventingand/or treating one or more infectious diseases of the hoof in animals,comprising: preparing a copper-free and zinc-free composition comprisingat least one cross-linking agent, wherein the cross-linking agent is notformaldehyde; and administering the composition to a lower leg and hoofarea of said animal to prevent and/or treat said one or more infectiousdiseases. Formaldehyde is the simplest and smallest aldehyde which undercertain conditions can make it effective, however dangerous.Di-aldehydes are a bit larger, less reactive, but exhibit goodcrosslinking because of their two aldehyde groups.

The cross-linking agents of the present invention are selected selectedfrom the group consisting of aldehydes, such as glyceraldehyde,glutaraldehyde, dextran dialdehyde, and carbohydrates; diols, such asethylene glycol, di(ethylene glycol), polyethylene glycol, propyleneglycol, di(propylene) glycol, polypropylene glycol; unsaturated diesterssuch as ethylene glycol dimethacrylate, di(ethylene glycol)dimethacrylate, poly(ethylene glycol) dimethacrylate, poly(laurylmethacrylate-co-ethylene glycol dimethacrylate), propylene glycoldimethacrylate, di(propylene glycol) dimethacrylate, polypropyleneglycol) dimethacrylate; dihydrazides such as malonic dihydrazide,ethylmalonic dihydrazide, succinic dihydrazide, glutaric dihydrazide,adipic dihydrazide, isophthalic dihydrazide, oxalyl dihydrazide, pimelicdihydrazide, 3,3′-sulfonyldibenzenesulfonic dihydrazide; diisocyanatessuch as m-xylylene isocyanate, 4-methyl-m-phenylene diisocyanate,2-methyl-m-phenylene diisocyanate, 3,3′-dimethoxy-4,4′-biphenylenediisocyanate, 4-Br-6-methyl-1,3-phenylene diisocyanate,4-Cl-6-methyl-1,3-phenylene diisocyanate, toluene 2,4-diisocyanate,1,3-phenylene diisocyanate, 1,4-phenylene diisocyanate,2,4,6-trimethyl-1,3-phenylene diisocyanate, 1,4-diisocyanatebutane,1,6-diisocyanatehexane, 1,8-diisocyanateoctane, isophorone diisocyanate;carbodiimides such as N,N-(3-dimethylaminopropyl)-N-ethyl carbodiimide(EDC); salts, such as CaCl.sub.2, divinylsulfone, sulfonylurea,hydrolysable polyrotaxane, L-lysine methyl ester, and genipin.Cross-linking may also be carried out or aided by one or more enzymes.

In another embodiment, the cross-linking agent is selected from thegroup consisting of glutaraldehyde, glyoxal, ortho-phthaldehyde,carbodiimides, diisocyanates, a formaldehyde donor, sodium hydroxymethylglycinate, diazolidinyl urea, imidazolidinyl urea,dimethylol-5,5-dimethylhydantoin, dimethylol urea,2-bromo-2-nitropropane 1,3-diol, quaternium-15, parabens,5-chloro-2-methylisothiazolin-3-one, 1,2-dibromo-2,4-dicyanobutane,ethanol and other alcohols, and polyol. In one embodiment, thecomposition of the present invention comprises glutaraldehyde, glyoxal,ortho-phthaldehyde or mixtures thereof.

Glutaraldehyde is a four carbon molecule terminated at both ends byaldehyde groups. It is widely used by light and electron microscopistsfor its efficacy in preserving cellular structure. It was conceived thatglutaraldehyde would be useful in the context of the present inventionbecause glutaraldehyde would not overly dry the treated area or causethe treated area or hooves to become brittle. Further, it was conceivedthat glutaraldehyde's comparatively high molecular weight would aid tolimit its ability to diffuse into the tissue, especially since as thetissue is cross-linked, its ability to penetrate over time diminishes.One of the added benefits of the presently taught composition is that itlimits the function of the composition to the superficial skin layerspreventing the composition from being too aggressive and penetrating toodeeply into the treated area. Moreover, whereas formaldehyde is known tocause chemical burns even to healthy tissue, use of glutaraldehyde asthe cross-linking agent of the presently taught composition allowsunscathed skin to remain healthy.

Penetration and diffusion rates for glutaraldehyde are very slow withtypical values of under about 5 mm of penetration on rat brainovernight. This is in sharp contrast to formaldehyde, which exhibitsfast penetration/diffusion rates but slow endpoint fixation rates. Itwas conceived that since manure/urine and mud slurry found on dairyfarms typically have a pH of around 8, a cross-linking agent such asglutaraldehyde would be effective, whereas such organic loading wouldessentially render formaldehyde and many other germicides ineffective.

Glutaraldehyde is a strong germicide and a cross-linking agent whichrapidly fixes or binds loose protein fibers. Glutaraldehyde is aneffective biocide and another of the advantageous properties of thepresent composition is that glutaraldehyde minimally penetrates into thetissue, thereby reducing the extent to which it may circulate in theblood stream and reach vital organs. Glyoxal is an organic compound usedas a solubilizer and cross-linking agent in polymer chemistry. It istypically supplied as a 40% aqueous solution.

The one or more cross-linking agents of the present invention arepresent in the composition at a level from 0.001% to 30%. In oneembodiment, the one or more cross-linking agents of the presentinvention are present in the composition at a level from 0.5% to 20%. Inanother embodiment, the one or more cross-linking agents of the presentinvention are present in the composition at a level from 1% to 15%. Inyet another embodiment, the one or more cross-linking agents of thepresent invention are present in the composition at a level from 1% to10%. In another embodiment, the one or more cross-linking agents of thepresent invention are present in the composition at a level from 5% to13%. In yet another embodiment, the one or more cross-linking agents ofthe present invention are present in the composition at about 10%. Inyet another embodiment, the one or more cross-linking agents of thepresent invention are present in the composition at about 25%. In oneembodiment, the one or more cross-linking agents of the presentinvention are present in the composition at a level from 5% to 30%. Inanother embodiment, the one or more cross-linking agents of the presentinvention are present in the composition at a level of about 40% toabout 50%.

In one embodiment, the composition of the present invention comprises anantimicrobial essential oil or an active thereof or mixture thereof,which contribute anti-microbial and bacterial properties to thecomposition. Suitable antimicrobial essential oils for use herein arethose essential oils which exhibit antimicrobial activity. By “activesof essential oils”, it is meant herein any ingredient of essential oilsthat exhibit antimicrobial activity. It is speculated that saidantimicrobial essential oils and actives thereof act as proteinsdenaturing agents.

Such antimicrobial essential oils include, but are not limited to, thoseobtained from thyme, lemongrass, citrus, lemons, orange, anise, clove,aniseed, pine, cinnamon, geranium, roses, mint, lavender, citronella,eucalyptus, peppermint, camphor, ajowan, sandalwood, rosmarin, vervain,fleagrass, lemongrass, ratanhiae, cedar and mixtures thereof.

Actives of essential oils to be used herein include, but are not limitedto, thymol (present for example in thyme, ajowan), eugenol (present forexample in cinnamon and clove), menthol (present for example in mint),geraniol (present for example in geranium and rose, citronella),verbenone (present for example in vervain), eucalyptol and pinocarvone(present in eucalyptus), cedrol (present for example in cedar), anethol(present for example in anise), carvacrol, hinokitiol, berberine,ferulic acid, cinnamic acid, methyl salicylic acid, methyl salycilate,terpineol, limonene and mixtures thereof. In one embodiment, thecomposition of the present invention comprises methyl salycilate.

Thymol may be commercially available for example from Aldrich—ManheimerInc, eugenol may be commercially available for example from Sigma,Systems—Bioindustries (SBI)—Manheimer Inc. In one embodiment, thecomposition further comprises a component selected from the groupconsisting of antimicrobial essential oils and actives thereof,quaternary ammonium compounds, paraben, aldehydes, phenolic compounds,alcohols, organic acids, chlorine-type bleaches, and mixtures thereof.

The antimicrobial essential oil or active thereof or mixture thereof ispresent in the composition at a level up to 20% by weight of the totalcomposition. In one embodiment, the level is at least 0.003% to 10%. Inanother embodiment, the antimicrobial essential oil or active thereof ormixture thereof is present in the composition at a level from 0.006% to10%. In another embodiment, the antimicrobial essential oil or activethereof or mixture thereof is present in the composition at a level from0.01% to 8%. In another embodiment, the antimicrobial essential oil oractive thereof or mixture thereof is present in the composition at alevel from 0.03% to 3%.

In one embodiment, the composition of the present invention comprisespropylene glycol or an equivalent thereof. In one embodiment, thecomposition of the present invention comprises a poly(alkylene glycol)alkyl ether, as defined herein after, or a mixture thereof. Suitablepoly(alkylene glycol) alkyl ethers for use herein include poly(propyleneglycol) mono butyl ether, poly(ethylene glycol-co-propylene glycol) monobutyl ether, poly(ethylene glycol) dimethyl ether, poly(ethyleneglycol-co-propylene glycol) dimethyl ether, poly(ethylene glycol)stearate or mixtures thereof. Poly(propylene glycol) mono butyl ether(average molecular weight 340) is commercially available from Aldrich orfrom Union Carbide under Ucon-lb 65.®.

Propylene glycol can serve as an anti-freeze. One advantageous propertyof the presently taught composition is that it is useful in coldclimates when traditional techniques for treating hairy heel warts faildue to cold weather. Colder temperatures are known to reduce theeffectiveness of formaldehyde and other agents, whereas glutaraldehyderetains its effectiveness in colder weather. Colder temperatures canalso cause freezing of footbaths containing conventional solutions.Propylene glycol can also serve as an emollient/skin conditioner used tocombat potential dryness that can result from the fixing agent.Propylene glycol also serves as a carrier and gelling agent like xanthamgum, albeit to a lesser extent.

The poly(alkylene glycol) alkyl ether or a mixture thereof is present inthe composition at a level from 0.001% to 10%. In one embodiment, thepoly(alkylene glycol) alkyl ether or a mixture thereof is present in thecomposition at a level from 0.3% to 3%. In another embodiment, thepoly(alkylene glycol) alkyl ether or a mixture thereof is present in thecomposition at a level from 0.005% to 2%. In yet another embodiment, thepoly(alkylene glycol) alkyl ether or a mixture thereof is present in thecomposition at a level from 0.01% to 1%. In another embodiment, thepoly(alkylene glycol) alkyl ether or a mixture thereof is present in thecomposition at a level from 0.05% to 0.5%.

In one or more embodiments of the present invention, the composition ofthe present invention includes about 0.1% to about 5% of a gellingagent. Suitable gelling agents include, in a non-limiting manner,naturally-occurring polymeric materials such as locust bean gum, guargum, sodium alginate, sodium caseinate, egg albumin, gelatin agar,carrageenin gum, sodium alginate, xanthan gum, quince seed extract,tragacanth gum, starch, chemically modified starches and the like,semi-synthetic polymeric materials such as cellulose ethers (e.g.hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose,hydroxy propylmethyl cellulose), hydroxypropyl guar gum, soluble starch,cationic celluloses, cationic guars and the like and synthetic polymericmaterials such as carboxyvinyl polymers, polyvinylpyrrolidone, polyvinylalcohol, polyacrylic acid polymers, polymethacrylic acid polymers,polyvinyl acetate polymers, polyvinyl chloride polymers, polyvinylidenechloride polymers and the like. In one embodiment, the gelling agent isxanthan gum.

Also useful herein are gelling agents such as the acrylic acid/ethylacrylate copolymers and the carboxyvinyl polymers sold, for example, bythe B.F. Goodrich Company under the trademark of Carbopol resins. Theseresins include a colloidal water-soluble polyalkenyl polyether crosslinked polymer of acrylic acid cross linked with from 0.75% to 2% of across linking agent such as polyallyl sucrose or polyallylpentaerythritol. Examples include Carbopol 934, Carbopol 940, Carbopol950, Carbopol 980, Carbopol 951 and Carbopol 981.

A gelling agent, for example, xanthan gum, acts as a thickener and apseudo-plasticizer which permits the composition of the presentinvention to thin out under stress to flow through a spray gun. Uponmaking contact with the wart, the composition gels and stays in place,allowing for greater contact time and making it more resistant torunoff. Since the treatment area involves regions of cows' hoof, whichby its nature is not stationary, this feature of the presently taughtcomposition is new and useful. Such gelling agents (e.g., xanthan gum,polymeric thickeners, cellulose thickeners, propylene glycol, glycerin,or the like) in the composition allow the composition to remain incontact with the infected area of the foot for a longer period of timethan a formulation without the thickener/gelling agent.

Xantham Gum would be classified as a gelling agent. It can thicken theaqueous solution and it was conceived that, with the gelling agent, onecan spray once a vertical plane and the solution will cling to thesurface and stick to the intended target. This is useful because thecomposition needs contact time (preferably at least about 4 minutes) toproduce successful results. In a wet, dirty environment, a more viscoussolution can adhere and keep more of the treatment solution on thetarget area. Xanthan gum also lowers the vapor pressure of the solution.Glutaraldehyde use at high concentrations could present potentialinhalation issues to workers, and the use of gelling agents like xanthamgum, and to some extent propylene glycol, acts as a carrier for theglutaraldehyde and prevents it from being atomizing into the air. In oneembodiment of the present invention, this property of the final productmakes the product user friendly and is beneficial and overcomes anypotential problem which could exist with use of glutaraldehyde or otherfixatives.

The composition of the present invention can include about 0.1% to about1% of a gelling agent. In another embodiment, the gelling agent ispresent in the composition at a level from 0.03% to 3%. In anotherembodiment, the gelling agent is present in the composition at a levelfrom 0.05% to 5%. In another embodiment, the gelling agent is present inthe composition at a level from 5% to 15%.

In one embodiment, the composition of the present invention comprisesquaternary ammonium compounds. Suitable quaternary ammonium compoundsfor use herein are quaternary ammonium compounds containing alkyl orsubstituted alkyl groups, alkyl amide and carboxylic acid groups, ethergroups, unsaturated alkyl groups, and cyclic quaternary ammoniumcompounds, which can be chlorides, dichlorides, bromides,methylsulphates, chlorophenates, cylcohexylsulphamates or salts of theother acids. Among the possible cyclic quaternary ammonium compounds arethe following: alkylpyridinium chlorides and/or sulphates, the alkylgroup being preferably cetyl, dodecyl or hexadecyl group;alkylisoquinolyl chlorides and/or bromides, the alkyl group beingpreferably dodecyl group. Particularly suitable quaternary ammoniumcompounds for use herein include octyl decyl dimethyl ammonium chloride,dioctyl dimethyl ammonium chloride, didecyl dimethyl ammonium chloride,alkyl dimethyl benzyl ammonium chloride, alkyl dimethyl benzyl ammoniumchloride wherein the alkyl is one or more of C₁₂ C₁₄ and C₁₆ alkyl,alkyl dimethyl ammonium saccharinate, cetylpyridinium and mixturesthereof.

The one or more quaternary ammonium compounds of the present inventionare present in the composition at a level from 0.001% to 30%. In oneembodiment, the one or more quaternary ammonium compounds of the presentinvention are present in the composition at a level from 0.5% to 20%. Inanother embodiment, the one or more quaternary ammonium compounds of thepresent invention are present in the composition at a level from 1% to15%. In yet another embodiment, the one or more quaternary ammoniumcompounds of the present invention are present in the composition at alevel from 1% to 10%. In another embodiment, the one or more quaternaryammonium compounds of the present invention are present in thecomposition at a level from 5% to 13%. In yet another embodiment, theone or more quaternary ammonium compounds of the present invention arepresent in the composition at about 10%. In yet another embodiment, theone or more quaternary ammonium compounds of the present invention arepresent in the composition at about 25%. In one embodiment, the one ormore quaternary ammonium compounds of the present invention are presentin the composition at a level from 10% to 30%.

In another aspect of the present invention, the composition includesand/or is used in combination with an effective amount of one or moresurfactants. The inclusion of the surfactant in the composition canimprove the performance of composition (e.g., improve wetting propertiesof the composition, stabilize components in the composition, function asan emulsifying agent, reduce filming and/or streaking). A variety ofsurfactants can be used in the composition. Such surfactants include,but are not limited to, nonionic, semi-polar, anionic, cationic,zwitterionic, and/or amphoteric surfactants. Many of these surfactantsare described in McCutcheon's Emulsifiers and Detergents (1997),Kirk-Othmer, Encyclopedia of Chemical Technology, 3rd Ed., Volume 22,pp. 332-432 (Marcel-Dekker, 1983), and McCutcheon's Soaps and Detergents(N. Amer. 1984), the contents of which are hereby incorporated byreference. Typically the surfactant is partially or fully soluble inwater.

In one embodiment, the surfactant includes, but is not limited to,glycoside, glycols, ethylene oxide and mixed ethylene oxide/propyleneoxide adducts of alkylphenols, the ethylene oxide and mixed ethyleneoxide/propylene oxide adducts of long chain alcohols or of fatty acids,mixed ethylene oxide/propylene oxide block copolymers, esters of fattyacids and hydrophilic alcohols, sorbitan monooleates, alkanolamides,soaps, alkylbenzene sulfonates, olefin sulfonates, paraffin sulfonates,propionic acid derivatives, alcohol and alcohol ether sulfates,phosphate esters, amines, amine oxides, alkyl sulfates, alkyl ethersulfates, sarcosinates, sulfoacetates, sulfosuccinates, cocoamphocarboxyglycinate, salts of higher acyl esters of isethionic acid, salts ofhigher acyl derivatives of taurine or methyltaurine, phenol poly ethersulfates, higher acyl derivatives of glycine and methylglycine, alkylaryl polyether alcohols, salts of higher alkyl substituted imadazoliniumdicarboxylic acids, ferchorics, tannics, naphthosulfonates,monochloracetics anthraflavinics, hippurics, anthranilics, naphthoics,phthalics, carboxylic acid salts, acrylic acids, phosphates, alkylamineethoxylates, ethylenediamine alkoxylates, betaines, sulfobetaines,and/or imidazolines.

In one aspect of this embodiment, the surfactant includes, but is notlimited to, lauryl sulfate, laurylether sulfate, cocamidopropylbetaine,alkyl polyglycosides, and/or amine oxides. In one embodiment, thesurfactant is selected from the group consisting of polyoxyethylenealcohols, alkyl ether sulfates, and alkyl sulfates. In one embodiment,the surfactant is an ethoxylated nonylphenol. CO 720 ethoxylatednonylphenol, for example, helps unwind the protein fibers, allowing themto be available for cross-linking. The CO 720 ethoxylated nonylphenolalso acts as an emulsifier for the methyl salicylate. Ethoxylatednonylphenol is a polyether. In another embodiment, the present aqueoussolution/composition of the present invention comprises one or morepolyethers.

CO 720 (ethodylated nonyl phenol) is a surface-active agent that wouldbe considered a surfactant. It prepares the surface to be treated sothat a fixing agent like glutaraldehyde can achieve greater penetration.This helps condition the surface by unwinding the tightly bound proteinsso that the glutaraldehyde or another cross-linking agent, for exampleanother di-aldehyde, can then crosslink using their two aldehyde groups.QUATS, quaternary ammonium compound, may also act as surfactants andwork in the same way when used in combination with a fixing agent likeglutaraldehyde. Bactericidal and fungicidal activities are due to thecombination of glutaraldehyde with metabolic enzymes and with theamino-acids. Being hydrophilic, glutaraldehyde cannot easily cross thecell's lipid membrane.

The one or more surfactants of the present invention are present in thecomposition at a level from 0.01% to 10%. In one embodiment, the one ormore surfactants of the present invention are present in the compositionat a level from 0.5% to 5%. In another embodiment, the one or moresurfactants of the present invention are present in the composition at alevel from 1% to 4%.

One aspect of the present invention is directed to a copper-free andzinc-free composition for the treatment and/or prevention of one or moreinfectious diseases of the hoof in animals, comprising at least onecross-linking agent, wherein said cross-linking agent is notformaldehyde. In one embodiment, the composition comprises about 5% toabout 30% by weight of at least one cross-linking agent; about 5% to 20%by weight of at least one quaternary ammonium compound; about 0.03% to3% by weight of at least one apoly(alkylene glycol) alkyl ether; about0.03% to 3% by weight of at least one gelling agent; about 0.03% to 3%by weight of at least one antimicrobial essential oil or active thereof;and about 0.03% to 5% by weight of at least one surfactant.

One aspect of the present invention is directed to a composition for thetreatment and/or prevention of one or more infectious diseases of thehoof in animals, comprising one or more cross-linking agents; one ormore quaternary ammonium compounds; one or more gelling agents; one ormore surfactants; one or more antimicrobial essential oils or activesthereof; and one or more poly(alkylene glycol) alkyl ethers.

One aspect of the present invention is directed to a method for treatingand/or preventing papilomatous digital dermatitis in an ungulate,comprising: preparing a copper-free and zinc-free composition comprisingat least one cross-linking agent and at least one quaternary ammoniumcompound; and spraying or applying in a foam a therapeutically effectiveamount of said composition to a lower leg and hoof area of said ungulatein order to treat and/or prevent said papillomatous digitial dermatitis.

In another aspect of the present invention, the composition includesand/or is used in combination with one or more biocides. Such biocidescan include, but are not limited to, alcohols, peroxides, boric acid andborates, chlorinated hydrocarbons, organometallics, halogen-releasingcompounds, mercury compounds, metallic salts, pine oil, organic sulfurcompounds, iodine compounds, silver nitrate, quaternary phosphatecompounds, and/or phenolics.

In one embodiment of the present invention the compositions may furthercomprise a pH buffer i.e. a system composed of a compound or acombination of compounds, whose pH changes only slightly when a strongacid or base is added. Suitable pH buffers and amount to use are knownto those skilled in the art. For example, suitable organic acids for useherein include monocarboxylic acids, dicarboxylic acids andtricarboxylic acids, acetic acid, citric acid, malonic acid, maleicacid, malic acid, lactic acid, glutaric acid, glutamic acid, asparticacid, methyl succinic acid, succinic acid or mixtures thereof. In oneembodiment, the citric acid and succinic acid or mixtures thereof areused.

The composition can be used at a range of effective concentrations. Insome embodiments, the composition has a pH of about 1.0 to about 6.0. Inother embodiments, the composition has a pH of about 1.0, about 1.5,about 2.0, about 2.5, about 3.0, about 3.5, about 4.0, about 4.5, about5.0, about 5.5, or about 6.0.

The compositions described herein can be contacted with an animalfoot/hoof in an amount effective to result in a reduction significantlygreater than is achieved by washing with water, or at least a 50%reduction, at least a 90% reduction, preferably at least a 99%reduction, in the resident microbial preparation.

The present methods usually require a certain minimal contact time ofthe composition with the foot/hoof of an animal for the treatment and/orprevention specified. The contact time can vary with concentration ofthe use composition, method of applying the use composition, temperatureof the use composition, amount of soil and/or contamination on the hoof,number of microorganisms present on the hoof, type and formulation ofthe disinfection composition, or the like.

The minimum exposure time to the presently taught composition is, forexample, at least about 2 to about 5 seconds. The exposure time can be,for example, at least about 15 seconds, at least about 30 seconds, atleast about 45 seconds, at least about one minute, at least about twominutes, at least about three minutes, at least about four minutes, atleast about five minutes, at least about six minutes, at least aboutseven minutes, at least about eight minutes, at least about nineminutes, at least about ten minutes, at least about 15 minutes, at leastabout 20 minutes, at least about 25 minutes, at least about 30 minutes,at least about 35 minutes, at least about 40 minutes, at least about 45minutes, at least about 50 minutes, at least about 55 minutes, or atleast about 60 minutes. In one embodiment, the exposure time to thepresently taught composition is between about 5 to about 30 minutes. Inone embodiment, the exposure time to the presently taught composition isbetween about 5 to about 120 minutes. Even longer exposure times arecontemplated, for example, several hours or even days. After directexposure during administration, it is contemplated that the disinfectioncomposition can remain in contact with a hoof for extended periods oftime. Generally, longer exposure times to the disinfection compositionwill be preferred as the pH increases.

Application of the composition to an animal's foot can occur in periodicapplications. An effective amount of the composition can be applied toan animal's foot several times per day and/or several times over aperiod of several days. For example, the composition can be applied topart or all of an animal's foot/hoof about every one hour, about everytwo hours, about every three hours, about every four hours, about everyfive hours, about every six hours, about every seven hours, about everyeight hours, about every nine hours, about every ten hours, about everyeleven hours, or about every twelve hours. Longer periods of timebetween applications are contemplated. For example, the composition maybe applied every day, every other day, every three days, or everyseveral days. In general, application of the present composition once ortwice on the same day or consecutive days has an effect.

It is contemplated that the presently taught composition can beadministered in the same or different form as a single dose or inmultiple applications. In some embodiments, a first composition and asecond antimicrobial composition are applied serially to the foot of ananimal. In some embodiments, a first concentrated composition is dilutedwith water to form a first antimicrobial composition, and a secondconcentrated composition is diluted with water to form a secondantimicrobial composition. The first and the second antimicrobialcomposition can be applied serially or jointly to a foot of an animal atpredetermined intervals. In some embodiments, the method for treating afoot of an animal comprises contacting a foot of an animal with any ofthe compositions taught herein. The compositions of the application canbe diluted in water to prepare for use. In one embodiment, thecomposition is diluted between about 10-fold to about 400-fold in waterbefore treating the foot of the animal. In an embodiment, thecomposition is diluted about 200-fold in water.

The composition may comprise additional components, including forexample skin conditioners, such as glycerin, propylene glycol, sorbitol,lanolin, derivates of polyethylene glycol (PEG)-lanolin andpolypropylene glycol (PPG)-lanolin, aloe vera, and allantoin, to promoteskin health and healing. Buffering agents may be used to adjust pH.Buffers may include organic acids, such as monocarboxylates, phosophoricacid, carbonates, and similar products. The pH may be adjusted by addingalkalinity such as sodium bicarbonate, sodium carbonate, sodiumhydroxide and potassium hydroxide. Film forming polymers may be used,including polyethylene glycol resins, polyvinyl alcohol, polyacrylates,polyvinyl pyrrolidinone, polyurethanes and corresponding copolymers.

The composition may also comprise antimicrobial agents such as quatbased antimicrobials, phenolics, peracids, hydrogen peroxide, acidifiedsodium chlorite, hypochlorous acid, iodine, chlorhexidine,aldehyde-based germicides, and fatty acids. Colorants selected fromgenerally recognized dyes and pigments may also be part of thecomposition. Any of these components may be used in various combinationsdepending on the desired features of a particular product.

The compositions and methods described herein, used alone or incombination with other known treatment compositions and modalities, canbe directed to the treatment and/or prevention of an infectious diseaseof the foot of an animal. The compositions and methods of the presentinvention have activity against a wide variety of microorganisms such asGram positive and Gram negative bacteria, yeast, molds, bacterialspores, and viruses. Treatments with any of the compositions of thepresent invention can be applied one time or repeatedly within a shortperiod of time (minutes or hours), or the treatments can be repeated asneeded over a longer period of time (days or months).

One aspect of the invention is directed towards treatment and/orprevention of one or more infectious diseases of a foot of an animal byadministration of the compositions described herein. Infectious diseasesof the foot of an animal that can be treated and/or prevented withcompositions and methods described herein include, but are not limitedto hairy heel warts, foot rot, and/or scald (foot rot includes, but isnot limited to, stable foot rot) or other conditions caused byFusobacterium necrophorum, Bacteroides melaminogenicus, and/orDiechelobacter nodosus. The term animal includes cattle, and thus bothcows and steers, as well as other animals and mammals.

In various embodiments, the animal to be treated is an ungulate. In oneembodiment, the subject of various treatments described herein is a cow,a sheep, a horse, or a goat. In another embodiment, the ungulate to betreated with the composition of the present invention is a cow.Infectious diseases in the hooves of cows are most prevalent in dairycow herds but are also problematic in beef cattle. The treatmentcompositions and methodologies described herein can be directed to dairyand/or beef cattle. In some embodiments, the ungulate to be treated witha composition of the present invention is a goat. In some embodiments,the ungulate to be treated with the composition of the present inventionis a horse. In other embodiments, the ungulate to be treated with anantimicrobial composition of the present invention is a sheep.

An animal foot can be contacted with a composition described herein byany method or apparatus suitable for applying the presently taughtcomposition. For example, although extensive studies were performedusing spray and foam formulations, it is contemplated that the presentlytaught composition may be administered by other means known to thoseskilled in the art. Various embodiments provides for components of thefootbath, spray, gel or foam form of the composition to be administeredsequentially. In other embodiments of the present invention, a footbath,spray, gel or foam form of the composition can be administeredsequentially with an antimicrobial composition in the same or anotherform such as a footbath, powder, spray, gel, or foam.

As stated supra, the solution described herein is specificallyformulated to be applied to the hooves and lower legs of the animal as aspray or foam formulation. Labor costs are a major concern to farmers.In one embodiment, an automated system is used to apply the solution, inorder to reduce labor costs. The automated system may use a programmabletime sequence and/or sensors that trigger dispensing. For example, in aspray application, sensors may be used to determine a presence of ananimal requiring treatment.

In one embodiment, it is contemplated that other means of applying thesolution as taught herein may achieve results that improve upon existingmethods of treating one or more diseases of the foot of an animal. Forexample, the taught solution herein may be used in a foot bathapplication, whether a traditional liquid solution or a foam, and aprogram may be used such that the treatment is dispensed into the troughat specific time intervals, and the old treatment solution isautomatically drained before dispensing the replacement treatmentsolution. Instead of a time interval, the system may monitor a number ofanimals that have passed through the trough and automatically replenishthe trough at a predetermined interval. Alternatively, sensors withinthe trough may be used to determine when the solution falls below apredetermined concentration (due to contamination in the trough) and/orwhen waste levels in the trough reach a specific level.

In another embodiment, the use of absorptive pads saturated with thecomposition may be used for treatment, however, wrapping with padsshould be loose. Generally, wrapping will prevent the formation of ascab, the rapid formation of which is facilitated by the presentlytaught methods and compositions, and which is necessary for healing.

For dairy cows, the treatment can be applied prior to entering a milkingparlor. Milking parlors are generally kept very clean, thus providingadequate time for contact between the solution and the skin and the hoofbefore returning to a potentially soiled environment. Alternatively, thetreatment may be applied as the cows exit the milking parlor such thatthe cows receive the treatment immediately prior to moving to a housingenvironment that may be dirty. The composition may be appliedperiodically, such as every day, every other day, or once a week.Generally, one or two applications either on same day or on consecutivedays facilitates formation of a scab.

In some embodiments, more than one application technique may be used incombination or multiple applications may be used. For example, a sprayfollowed by foam may be used in series, or a foot bath followed by aspray or foam administration. The first foot bath may contain adetergent solution to remove dirt and manure from the hooves; the secondspraying or foaming containing the solution as taught herein. In anotheraspect of the invention, a rotation of treatments may be used. In oneembodiment of the present invention, the affected area is first cleaned,for example washed with water or by a first pass through a footbath, toclear the mud and manure for example and provide good exposure of thelesion to the to-be administered composition of the present invention.

6.3 FORMULATIONS

The present invention includes any known application technique fordelivering an composition to the lower leg and hoof of the animal. Theapplications include, but are not limited to, foam, direct spraying, andpropellant spray. In one embodiment, an automated system, as describedfurther below, is used for applying the composition to the animals.

Foot baths are currently the most common application mode for treatinghairy heel warts and other hoof related diseases. Cows are directed towalk through troughs containing the liquid treatment. A disadvantage offoot baths is that the liquid treatment may easily become contaminateddue to organic waste from the cows. In some cases the foot bath may evenbecome a vehicle for transferring bacteria to other cows. Foot bathsthus may require frequent replenishment, as well as significant laborcommitments in some cases.

6.3.1. Spray

As an alternative to a foot bath, the composition may be sprayed on thehooves. An advantage of a spray application is that a fresh treatment isapplied to each cow, as compared to a foot bath application which maybecome contaminated over time. In some embodiments, a worker mayindividually spray each cow as the cow is on its way into or out of themilking parlor. Alternatively, an automated system may be used to spraythe treatment onto the hooves.

In various embodiments, the compositions described herein can beadministered as a spray. In one embodiment, the presently taughtcompositions are sprayed onto the lesion so as to adequately cover thelesion. Depending on the lesion size, this can take about 3 ml to about10 ml of the composition being sprayed onto the lesion. The compositionscan be applied using fixed or articulating nozzles, at higher pressures,varying or steady flow rates, various temperatures, and/or with orwithout agitation or brushes. Spraying can be accomplished by anapparatus such as a spray cabinet with stationary or moving spraynozzles. The nozzles can create a mist, vapor, or spray that contacts ananimal's feet. The spray can be set up as a walk-through pen or in aholding pen. In one embodiment, the composition as taught herein isapplied either with the 32 oz hand pump sprayer or a larger pumpsprayer. In one embodiment, the composition is a thinner formulationused to spray either the entire herd or individual warts, named HealMaxHerd Spray.

Application of a material by spray can be accomplished, for example,using a manual spray wand application, an automatic spray of the animalsmoving through a gate or room or gateway, or the like. Multiple sprayheads to ensure complete contact or other spray means may be used. Inone embodiment, an automatic spray application is used, involving theuse of a spray booth. The spray booth substantially confines the sprayedcomposition to within the parameter of the booth. The spray booth caninclude steam jets that can be used to apply the compositions of thepresent invention. The spray pattern can be virtually any useful spraypattern.

When using a spray application, additional components may be included inthe composition to enhance application of the solution onto the skin andhooves. In some embodiments, thickeners may be used to retain a greaterquantity of liquid per skin area. Surfactants may also be used incombination with or as an alternative to thickeners. The surfactantsreduce the surface tension of the aqueous composition on the skin andthus help the solution to wet and spread over the skin. The compositionalso may contain film forming polymers that dry to a second skin to helpin holding the composition to the skin or to provide a protectivebarrier to the skin.

In some embodiments, a thickener is used in a spray application toincrease a viscosity of the composition. In other embodiments, theviscosity of the composition is equal to or greater than approximately20 centipoise for spray applications. Suitable thickeners may includepolymeric thickeners, clays, silicas, and associative thickeners.Moreover, surfactant thickened systems may be used to form ancomposition having the desired viscosity for spraying the compositiononto the hooves and lower legs of an animal. A propellant spray also maybe used to apply a composition to the hooves and lower leg area. Thepropellant spray typically requires the use of volatile propellants.

6.3.2. Other

In additional embodiments, the composition taught herein may be appliedas a foam. The foam may be applied in two ways. The foam may bedispensed into a trough and the cows may then walk through the foam,similar to a liquid foot bath. Alternatively, the foam may be applieddirectly to the hooves using any known foam dispensing technique. In oneembodiment, where a flash foamer is added to this spray, the product mayeffectively be foamed onto warts, with the use of a foam sprayer. Thepresently taught foam composition, named HealMax Foam, is an effectivetreatment method because, inter alia, the foam provides improvedaccuracy and the foam increases contact/treatment time.

The foam can be prepared, for example, by mixing foaming surfactantswith the composition. The foaming surfactants can be nonionic, anionic,or cationic in nature. Examples of useful surfactant types include, butare not limited to the following: alcohol ethoxylates, alcoholethoxylate carboxylate, amine oxides, alkyl sulfates, alkyl ethersulfate, sulfonates, quaternary ammonium compounds, alkyl sarcosines,betaines, and alkyl amides. The foaming surfactant is typically mixed attime of use with the composition but can be prepared in advance of thetime of use. At time of use, compressed air can be injected into themixture, and the foam can be applied to a foot of an animal.

Thickeners (e.g., xanthan gum, polymeric thickeners, cellulosethickeners, propylene glycol, glycerin, or the like) can be furthercombined to produce a foam which may remain in contact with the infectedarea of the foot for a longer period of time than a formulation withoutthe thickener. In some embodiments, a foam antimicrobial compositioncontains about 5 wt % to about 20 wt % of one or more thickeners. In afoam application, two important parameters include the density of thefoam (i.e. how much liquid per unit volume) and the stability of thefoam (specifically, a drainage rate of the foam). In one embodiment, thefoam is intrinsically viscous and allows greater foam stability. Forfoam applications, an appropriate viscosity range for the composition isbetween approximately 14 and 100 centipoise. Many of the same featuresthat beneficial to a spray application may also be useful in a foamapplication. For example, surfactants and thickeners may both be used toimprove foam properties.

The foamed composition, according to one or more embodiments of thepresent invention, is of exceptionally low specific gravity, forexample, the foamed composition has a specific gravity in the range ofabout 0.02 gr/ml to about 0.35 gr/ml. Although of low specific gravity,the foam is highly stable and will remain without collapse for severalminutes. Nonetheless, the foam collapses readily upon application ofmild shear stress. Low specific gravity, high foam stability and readycollapsibility all contribute to a foamed composition that is easilyapplied and administered over large areas without rubbing or chaffing ofthe affected area. A foam adjuvant is included in the composition toimprove the stability and reduce the specific gravity of the foamedcomposition. In one or more embodiments of the present invention, foamadjuvants include fatty alcohols, fatty acids, and mixtures thereof. Thefoam adjuvant can include at least one fatty alcohol and at least onefatty acid.

The foamed composition, according to one or more embodiments of thepresent invention, is dispensed from a glass or plastic container thatdispenses foam in the absence of a gas or liquid propellant.Alternatively, the composition of the present invention further includesa liquefied or compressed gas propellant at a concentration of about 3%to about 25% of the total composition. Examples of suitable propellantsinclude volatile hydrocarbons such as butane, propane, isobutane ormixtures thereof, and fluorocarbon gases. In another embodiment, thecomposition according to one or more embodiments of the presentinvention is preferably placed, together with a liquefied or compressedgas propellant in the amount of about 3% to about 25% of the totalcomposition, in an aerosol container. Upon pressing the actuator, abreakable foam, suitable for topical administration is released.

In other embodiments, the composition can be administered as a gel. Theanimal's foot can be treated with a thickened or gelled version of thecomposition. In the thickened or gelled state, the composition canremain in contact with the animal's foot for longer periods of time,thus increasing the antimicrobial efficacy. The thickened or gelledsolution can also better adhere to vertical surfaces and crevices in theanimal's foot. The composition can be thickened or gelled using one ormore thickening agents including, but not limited to, xanthan gum,polymeric thickeners, cellulose thickeners, propylene glycol, glycerin,or the like. The thickeners or gel forming agents can be used, forexample, in the concentrated product or by mixing with the antimicrobialcomposition at time of use. Exemplary use levels of thickeners or gelagents can range from about 100 ppm to about 10%, by weight.

In one embodiment, a footbath is used. Immersing an animal's foot in theaqueous solution of the present invention can be accomplished by any ofa variety of methods known to those of skill in the art. For example,troughs can be used to immerse the feet. The composition of the presentinvention, contained in the trough, can be agitated so as to increasethe application and/or absorption of the solution into or onto the feet.Agitation can be obtained by conventional methods, includingultrasonics, aeration by bubbling air through the solution, bymechanical methods, such as strainers, paddles, brushes, pump drivenliquid jets, or by combinations of these methods. The composition can beheated to increase the efficacy of the solution in killingmicroorganisms. After the foot has been immersed for a time sufficientfor the desired effect, the foot can be removed from the bath and theantimicrobial composition can be rinsed, drained, blotted, or evaporatedfrom the foot. Treatments with any of the compositions of the presentinvention can be applied one time or repeatedly within a short period oftime (minutes or hours), or the treatments can be repeated as neededover a longer period of time (days or months).

6.4 KITS

In various embodiments, the present invention can also involve kits foruse in the treatment of an infectious disease of a foot of an animal.Such kits can include the presently taught compositions and, in certainembodiments, instructions for administering and/or using thecomposition. When supplied as a kit, the different components of thecomposition can be packaged in separate containers and admixedimmediately before or during use. Such packaging of the componentsseparately can, if desired, be presented in a pack or dispenser devicewhich may contain one or more unit dosage forms containing thecomposition. Such packaging of the components separately can also, incertain instances, permit long-term storage without losing activity ofthe components. In various embodiments, the different components can bepackaged in one composition for administration together.

In certain embodiments, the concentrates may be sold as a kit, whichincludes instructions for mixing the concentrates to form a compositionwith appropriate properties. Instructions may be printed on paper orother substrate, and/or may be supplied as an electronic-readablemedium. Detailed instructions may not be physically associated with thekit; instead, a user may be directed to an internet web site specifiedby the manufacturer or distributor of the kit. As an example, theinstructions may include instructions for forming a solution having aspecific concentration and/or instructions to adjust a pH level of thecomposition.

Having described the invention in detail, it will be apparent thatmodifications, variations, and equivalent embodiments are possiblewithout departing the scope of the invention defined in the appendedclaims. Furthermore, it should be appreciated that all examples in thepresent disclosure are provided as non-limiting examples.

7. EXAMPLES

The following non-limiting examples are provided to further illustratethe present invention. It should be appreciated by those of skill in theart that the techniques disclosed in the examples that follow representapproaches the inventors have found function well in the practice of theinvention, and thus can be considered to constitute examples of modesfor its practice. However, those of skill in the art should, in light ofthe present disclosure, appreciate that many changes can be made in thespecific embodiments that are disclosed and still obtain a like orsimilar result without departing from the spirit and scope of theinvention.

7.1 Example 1 HealMax Wart Spray I Development and Field Testing

HealMax HealMax Wart Spray I (%) Herd Spray (%) Glutaraldehyde 50% 25 25Deionized Water 69.34 69.68 C.O. 720 (ethoxylated nonyl phenol) 2.602.60 Methyl Salicylate 1.35 1.35 Propylene Glycol 1.35 1.35 Xanthan Gum0.34 — Green Dye 0.02 0.02

A trial was conducted on a 500 cow commercial Holstein dairy in Hanford,Calif. (Fragosa & Sons) which was experiencing a rapid outbreak ofdigital dermatitis. Dairy had been using an acidified copper sulfatefootbath once a day for 4-5 days per week. 10% of dairy cows (50) showedsigns of clinical lameness due to advanced digital dermatitis lesions. Aqualified hoof trimmer, using a trimming chute, inspected and selected 5cows with visible lesions due to digital dermatitis. These cows were notallowed to pass through the regular footbath during the 4 day trialperiod.

Lesion Severity: The severity of each lesion was scored as follows: 0 Novisible lesion. 1 Early Stage: Skin slightly broken, redness,inflammation. 2 Moderate Stage: Visible open lesion, redness,inflammation, some blood. 3 Advanced Stage: Visible open lesion,redness, inflammation, very bloody.

Lameness: Each cows locomotion was observed and assigned a lamenessscore as follows: 0 No visible lameness 1 Slight Lameness. Noticeablewhile walking. 2 Moderate/Severe Lameness. Difficulty walking, visiblylifting leg to reduce weight.

A control group of 5 cows was chosen and ranked according to the samecriteria as the test group. This group was allowed to walk through theregular daily footbath treatment consisting of acidified copper sulfate.Cows were milked three times per day and the foot bath was operated forone milking per day.

Each treatment of HealMax Herd Spray was applied while the cow wasimmobilized in a trimming chute. Each lesion was cleaned of debris withwater, photographed, and then sprayed with enough of the presentlytaught composition to completely cover the lesion. Treatment dosageaveraged 4-6 spays or 4-6 ml of product. In one embodiment, it isconceived that about 10 ml to about 20 ml of the composition isadministered by spray or foam to the hoof. Each cow was then given 5minutes to lay idle before being released from the trimming chute.

After 4 days both the test group and control group were sequestered fromthe herd and examined by the same hoof trimmer while on the trimmingchute. Each lesion was then ranked to determine the treatment effectaccording to the following criteria:

(−2) Lesion significantly increased in size and severity. AdditionalTreatment Required. (−1) Lesion increased in size and severity.Additional Treatment Required. (0) No visible signs of improvement.Lesion stayed about the same size and severity. Additional TreatmentRequired. (+1) Lesion shows slight signs of improvement. Some whitescabbing. Redness and/or visible blood. Additional Treatment Required.(+2) Lesion shows significant signs of improvement. White and/or blackscab formation. Some redness visible. Additional Treatment Optional.(+3) Lesion shows dramatic signs of improvement. White and/or blackscab. No additional treatment required.

Post treatment lesion severity was observed and ranked according to theinitial criteria:

0 No visible open lesion. 1 Early Stage: Skin slightly broken, redness,inflammation. 2 Moderate Stage: Visible open lesion, redness,inflammation, some blood. 3 Advanced Stage: Visible open lesion,redness, inflammation, very bloody.

Test Group—showed a significant improvement in all test cows that weretreated with the presently taught composition (see FIG. 5 and tablebelow). After about five days, the warts were mostly healed and theanimals were able to walk and feed normally. Administration of thepresently taught spray composition created darkened waterproof scabs,which sealed off the open warts. 4 out of 5 cows required no furthertreatment due to complete and thorough scabbing of lesions. Only Cow 251which had a severe lesion prior to treatment required one additionaltreatment. Lameness post treatment decreased for each cow. Applicationof a second spray after one or two days of the first spray applicationshowed great effect on severely affected animals.

Control Group (Acidified Copper Sulfate Footbath)—Lesions eitherincreased in severity or stayed the same with no perceptible difference.Lesions with an initial severity rating of 2 or 3 tended to increase inseverity while lesions with an initial severity rating of rated 1 or 2stayed about the same or slightly increased in severity. Lameness posttreatment either stayed the same or increased. This result wasconsistent with copper sulfate footbaths during an outbreak of digitaldermatitis. Typically, larger and severe warts tend to get worse, whilesmaller less established warts either get worse or stay the same.

Cow Severity - Treatment Severity - Post Lameness - # Initial LamenessEffect Treatment Post Test Group HealMax Wart Spray, 1 application 89 32 (+3) 0 0 251 3 2 (+2) 1 1 667 3 2 (+3) 0 0 524 2 2 (+3) 0 0 72 2 1(+3) 0 0 Control Group Acidified Copper Sulfate, once per day, 4 days376 2 1 (−2) 3 2 492 3 2 (−1) 3 2 27 3 2 (−1) 3 2 399 2 1 0 2 1 602 1 10 1 1

7.2. Example 2 Cross-Linking Tests and Development of HealMax Wart SprayII

Components HealMax Wart Spray II (%) Glutaraldehyde 50% 8.3 Glyoxal 40%16.66 C.O. 720 2.60 (ethoxylated nonyl phenol) Methyl Salicylate 1.35Propylene Glycol 1.35 Polymer gum 0.50 QUAT BTC855 10.00 Deionized WaterBalance

Additional experiments were conducted in order to further develop aproduct, optionally using substantially less glutaraldehyde, but withthe same or better performance than the presently taught novel HealMaxWart Spray I. It was conceived that such a novel composition for theprevention and/or treatment of one or more infectious diseases of thehoof in animals could be formulated by using less glutaraldehyde inorder to reduce the cost and any other potential issue associated withuse of higher concentrations of glutaraldehyde. The components used wereGlutaraldehyde (Dow, BASF), C0720 (Rhodia, Huntsman), methyl salicylate(Polarome), propylene glycol (Dow), xanthan gum (AEP Colloids) and greendye (Sensient by Prime Ingredients).

By reducing the amount of glutaraldehyde to less than 5% resulted insignificantly less cross-linking of test samples (see FIG. 2).Furthermore, actual application of such a low concentration ofglutaraldehyde on digital dermatitis lesions showed that theconcentration was ineffective at facilitating adequate scab formation inan acceptable time span. Unlike fixation of microscopy samples orsterilization of instruments using glutaraldehyde, there is a limitedamount of time on a dairy farm in which to achieve acceptable results.This time generally corresponds with 5-10 minutes that milking cowsspend in the relatively clean environment of a milking parlor forexample. After that time period, cows are released into a significantlydirtier and often wetter environment where they quickly step in a mud,manure, urine, and water mixture known as “Slurry”. Therefore, rapidformation of the scab is necessary. In one embodiment of the presentinvention, after spraying or foaming of the presently taughtcomposition, a scab forms within about five to about fifteen minutes.

Several di-aldehydes with properties similar to glutaraldehyde wereconsidered for their ability to cross-link samples. Glyoxal was selectedbecause it is the smallest di-aldehyde molecule and it was conceivedthat this would provide a desired efficacy in the context of germicidal(cross-linking) ability. Glyoxal has bactericidal properties comparablewith those of glutaraldehyde and is also used as a bactericide inpreparation with other components. The bifunctionality of glyoxal isused to cross-link functionalized macromolecules such as cellulose,polyacrylamides, polyvinyl alcohol, keratin and other polycondensates.Results on biodegradation are available, showing that glyoxal is clearlyreadily biodegradable. In one embodiment of the present invention, thecomposition as taught herein is a biodegradable product.

Given these characteristics, glyxol was chosen as a suitable replacementand testing commenced with glyoxal as a sole substitute. As shown onFIG. 3, glyoxal alone did produce cross-linking effects, however, at alow level (2.5 maximum). Next, it was conceived that a 2:1 ratio ofglyoxal-glutaraldehyde would be effective when compared to eithercomponent alone. A quaternary ammonium compound, QUAT, was also testedwith the 2:1 ratio of glyoxal-glutaraldehyde. It was surprisingly foundthat the combination of the 2:1 ratio of glyoxal-glutaraldehyde coupledwith QUAT at 10% achieved highly desirable results as seen on the graph(see FIG. 4). This novel composition achieved a high degree and rapidrate of cross-linking, as indicated in FIG. 4. Further testing in thefield showed that this new composition effectively facilitates scabbingand effectiveness similar to that of HealMax Wart Spray I.

Tests were performed in order to obtain a skin (crust) on the proteinmedium by using a cross-linking agent. Time, temperature and skimformation were monitored. Tests were performed at 40° F.—both medium andsolutions were cooled to test temperature. Test medium was prepared bymixing a solution containing 85% D.I. water and 15% Hydrolyzed BovineDry Collagen (purchased from Milligan & Higgens). Approx 4 oz of thepreparation was put into Petri dishes, placed in a refrigerator forthirty minutes before reacclimatizing at room temperature, ready fortesting. Subsequently, the various test solutions were poured into 4 ozbottles with spray nozzles and 10 ml of solution was sprayed onto themedium in the petri dishes from a distance of 6 inches, timed and viewedat 15 minute intervals and the contents of the petri dish was thenscored for skin formation. The time and extent of skin formation wasnoted and transposed to graphs (see FIGS. 1-4).

A second series of tests were run using Egg Albumin Powder (purchasedfrom J. T. Baker) as the protein medium, prepared by mixing 85% D.I.water and 15% Egg Albumin Powder. Both test produced identical results.

Lab testing was performed to assess cross-linking ability of variouscompositions. Various cross-linkers were tested, including formaldehyde(see FIG. 1), glutaraldehyde (see FIG. 2), glyoxal (see FIG. 3), and aunique combination of components (see FIG. 4). Varying percentages ofglutaraldehyde, formaldelhyde, glyoxal and the combination of componentswere sprayed onto the test medium in Petri dishes and compared atfifteen minute time intervals. The total test time was two to threehours.

The amount of xanthan gum to be added was determined by testing variouspercentages of gum sprayed through a hand spray gun. HealMax Wart Spraywas sprayed onto a vertical surface and the degree of cling and run wasmeasured. Various temperatures were tested between 40 and 90 degrees F.in order to be sure that temperature did not affect the sprayingability.

The scoring for the skin formation was as follows:

Extent of skin formation (Scored from 0 to 10) Properties of proteinmedium 0-2 very watery, lack of visible skin formation, unchanged color3-4 very thin skin formation, slight pale yellow color change 5-6 thinto moderate skin formation, pale to light yellow color change 7-8 firmskin, approx 2-3 mm thickness, medium yellow color 9-10 very firm skin,approx 3 mm thick, medium to dark yellow color

7.3 Example 3 Field Testing

HealMax Foaming Herd Spray was tested at Legacy Farm LLC, Plainview Tex.where an outbreak of hairy heel warts was occurring. Approximately 1000cattle were treated with a power foamer and HealMax Foaming Herd Spray.Of these 1000 cattle, approximately 9% of the herd exhibited hairy heelwart lesions of various degrees of severity. 30% of cows with hairy heelwarts lesions were in advanced stages classified as severe, 45%exhibited lesions that were moderately severe, and 25% of lesions werein the early stages. The foam was applied directly to open wart lesionscaused by digital dermatitis while cattle walked to the milking parloras well as to hooves that were unaffected by lesions. Foam was appliedfor two consecutive days.

The results showed an overall 81% elimination in hairy heel wart lesionswhen evaluated by the Hoof Trimmer one week after the second applicationof the foam with the remaining cows requiring an additional treatment.Of the 19% that required additional treatment, these cows exhibited themost severe heal wart lesions, in some cases with lesions on more thanone leg, yet even these cows exhibited post treated lesions that wereeither partially scabbed or reduced in size. One or two additionalproduct applications would constitute an additional treatment needed tofully scab and therefore complete the enclosure of the open lesion.

Moreover, of the 910 cows that were treated but did not have hairy heelwart lesions, there were no reports of new heal wart lesions of anystage of severity. Of the 27 cows with severe hairy heel wart lesions, 8cows (30% of severe group) required further treatment to ensure completeclosure of the lesion, the remaining cows exhibited closed, scabbedlesions, requiring no further treatment. Of the 40 cows with moderatelysevere lesions, 6 cows (15% of moderately severe group) required furthertreatments while the remaining 36 cows showing closed, scabbed, lesions.Of the 23 cows with early stage hairy heel wart lesions, 3 cows (13% ofearly stage) required further treatment.

These results demonstrate that, similar to application via spray,application of the presently taught composition via foam is an effectivemeans to treat and/or prevent one or more infectious diseases of thehoof in animals, including hairy heel warts. Unlike the first producttrial, these cows were treated during regular production versus beingsequestered and then treated on a trimming table. The lesions and hooveswere initially sprayed with water from a hose but at a proximity thatwould not ensure all dirt and debris were cleared from the lesion.Furthermore, because the cows were standing, it was difficult to clearall debris and likewise it was more challenging to ensure completeproduct coverage. Nonetheless, the results demonstrate that the productis highly effective when used during the daily production routine fortreatment and/or prevention of an active infectious disease, such ashairy heel warts.

The effectiveness of HealMax Foaming Herd Spray was found to at leastapproximately parallel HealMax Herd Spray, albeit the foam applicationmethod for the customer was better suited for their dairy operation.Large dairy operations benefit from foaming the product because it canbe integrated into their milking routine, foaming uses less product,increased accuracy in achieving thorough contact with lesion. Also,dairy farm management can quickly see that cows are being properlytreated with Healmax by the milking staff. The foam may be able tobetter handle dirt and debris because the foam has additional cling andcontinues to deliver fresh product as the foam breaks down into liquid.

Application of HealMax Foaming Herd Spray allows, inter alia, for moreaccurate application due to visibility, less product usage, and theability to treat areas difficult to reach such as underneath the hoof orbetween cloves of the hoof. Foaming is safe because it reduces theopportunity for a highly concentrated stream of product with stickingcapability to hit a worker in the face/eye. Although no direct detailedcomparison experiments were done to compare the presently taught sprayformulation with the presently taught foam formulation, given thatsimilar to the spray formulation the foam works highly effectively, onewould expect the results of HealMax Foam to be the similar if not thesame as those observed with HealMax Spray formulations. This would beexpected so long as a similar if not identical concentration of activeingredient was used and a similar application protocol was used of firstcleaning the treatment region with water and allowing 5-10 minutes ofapplication time after initial contact.

7.4 Example 4 Addition of Anaesthetic

Trials are conducted where a numbing agent is added to the novelcomposition taught herein. The numbing agent, Lidocaine, at the rate of2.5% is added to the formulation. HealMax may sting for several minuteswhen applied to an open sore. While stinging is much less severe thanother products such as acidified copper, in some cases, it may agitatethe cow thus causing it to kick or move more than normal. This couldcause potential harm to the individual spraying or if in the milkingparlor the milking equipment could be knocked loose from the udders.Testing of a formulation which includes a numbing agent, Lidocaine, toreduce stinging sensation is carried out. A stable HealMax solution withthe addition of lidocaine hydro chloride monohydrate USP at the rate ofaddition of 2.5% has been produced. This product is tested to determineif stinging sensation is mitigated by the addition of a numbing agentsuch as lidocaine. This is accomplished by observing the comfort levelof a cow directly after spraying. The numbing agent has a beneficial anddesirable effect because, inter alia, it numbs the treated site andreduces any pain or irritation caused to the ungulate by application ofthe presently taught compositions.

The invention claimed is:
 1. A copper-free and zinc-free composition forthe treatment of an animal that has or is at risk of having one or moreinfectious diseases of the hoof in animals, comprising at least onealdehyde, wherein said cross-linking agent is not formaldehyde.
 2. Thecomposition of claim 1, wherein said infectious disease of the foot ishairy heel warts, foot rot, stable foot rot, or foot scald.
 3. Thecomposition of claim 1, wherein said aldehyde is selected from the groupconsisting of glyceraldehyde, glutaraldehyde, dextran dialdehyde, andcarbohydrates.
 4. The composition of claim 1, wherein the compositionfurther comprises at least one antimicrobial essential oil or at leastone active thereof or a mixture thereof.
 5. The composition of claim 1,wherein the composition further comprises at least one poly(alkyleneglycol) alkyl ether.
 6. The composition of claim 1, wherein thecomposition further comprises at least one gelling agent.
 7. Thecomposition of claim 1, wherein the composition further comprises atleast one quaternary ammonium compound.
 8. The composition of claim 1,wherein the composition further comprises at least one surfactant. 9.The composition of claim 1, wherein the composition further comprisesone or more ethoxylated nonlyphenols.
 10. The composition of claim 1,wherein said composition comprises about 5% to about 30% by weight of atleast one aldehyde; about 5% to 20% by weight of at least one quaternaryammonium compound; about 0.03% to 3% by weight of at least onepoly(alkylene glycol) alkyl ether; about 0.03% to 3% by weight of atleast one gelling agent; about 0.03% to 3% by weight of at least oneantimicrobial essential oil or active thereof; and about 0.03% to 5% byweight of at least one surfactant.
 11. A composition for the treatmentof an animal that has or is at risk of having one or more infectiousdiseases of the hoof in animals, comprising one or more aldehydes,excluding formaldehyde; one or more quaternary ammonium compounds; oneor more gelling agents; one or more surfactants; one or moreantimicrobial essential oils or actives thereof; and one or morepoly(alkylene glycol) alkyl ethers.
 12. A composition for the treatmentof an animal that has or is at risk of having one or more infectiousdiseases of the hoof in animals, comprising glutaraldehyde and glyoxal,wherein said composition is substantially free of formaldehyde, copperand zinc.
 13. The composition of claim 12, wherein said infectiousdisease of the foot is hairy heel warts, foot rot, stable foot rot, orfoot scald.
 14. The composition of claim 12, wherein the compositionfurther comprises at least one antimicrobial essential oil or at leastone active thereof or a mixture thereof.
 15. The composition of claim12, wherein the composition further comprises at least one poly(alkylene glycol) alkyl ether.
 16. The composition of claim 12, whereinthe composition further comprises at least one gelling agent.
 17. Thecomposition of claim 12, wherein the composition further comprises atleast one quaternary ammonium compound.
 18. The composition of claim 12,wherein the composition further comprises at least one surfactant. 19.The composition of claim 12, wherein the composition further comprisesone or more ethoxylated nonlyphenols.
 20. The composition of claim 12,wherein said composition comprises about 5% to about 30% by weight ofglutaraldehyde and glyoxal; about 5% to 20% by weight of at least onequaternary ammonium compound; about 0.03% to 3% by weight of at leastone poly(alkylene glycol) alkyl ether; about 0.03% to 3% by weight of atleast one gelling agent; about 0.03% to 3% by weight of at least oneantimicrobial essential oil or active thereof; and about 0.03% to 5% byweight of at least one surfactant.